Sensitization of 9L rat brain gliosarcoma cells to 1,3-bis(2-chloroethyl)-1-nitrosourea by alpha-difluoromethylornithine, an ornithine decarboxylase inhibitor.
alpha-Difluoromethylornithine, a known inhibitor of polyamine biosynthesis, significantly enhanced the cytotoxic effect of 1,3-bis(2-chloroethyl)-1-nitrosourea, a cell cycle-nonspecific agent, in 9L rat brain gliosarcoma cells in vitro. Administered as a single agent, alpha-difluoromethylornithine was not cytotoxic to 9L cells and, compared to untreated control cells, caused no perturbation of cell cycle kinetics. alpha-Difluoromethylornithine-induced depletion of intracellular polyamine levels appears to have caused the observed sensitization of 9L cells to 1,3-bis(2-chloroethyl)-1-nitrosourea. Restoration of intracellular polyamine levels by the addition of exogenous putrescine to treated 9L cells reversed this phenomenon.
D000818:Animals; D001932:Brain Neoplasms / Q000473:pathology*; D002330:Carmustine / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D000518:Eflornithine; D005910:Glioma / Q000473:pathology*; D007700:Kinetics; D009952:Ornithine / Q000031:analogs & derivatives* / Q000494:pharmacology; D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines / Q000378:metabolism; D011700:Putrescine / Q000494:pharmacology; D051381:Rats
D065108:Ornithine Decarboxylase Inhibitors; D011073:Polyamines; D009952:Ornithine; D002330:Carmustine; D011700:Putrescine; D000518:Eflornithine